TOPLINE:

Patients with primary adrenal insufficiency had a higher risk for all-cause mortality than the general population or control individuals without the condition, with cardiovascular disease being a major cause of death. The risk for mortality was slightly higher among those with congenital adrenal hyperplasia.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of observational studies to assess the risk for mortality in patients with primary adrenal insufficiency, including those with congenital adrenal hyperplasia.
• They included seven population-based or case-control studies reporting long-term all-cause mortality outcomes in 9876 patients compared with those in a reference population (general population or control individuals without the condition).

TAKEAWAY:

• A meta-analysis of four studies involving 5750 patients showed that those with primary adrenal insufficiency had a higher risk for all-cause mortality than control individuals (pooled hazard ratio [HR], 2.51; 95% CI, 1.47-4.31).
• A pooled meta-analysis of three studies involving 4126 patients, excluding those with congenital adrenal hyperplasia, suggested a trend towards an increased risk for all-cause mortality in patients with primary adrenal insufficiency vs the general population (standardised mortality ratio, 2.49; 95% CI, 0.99-6.28).
• In a subgroup analysis of three studies exclusively involving 3698 patients with congenital adrenal hyperplasia, all-cause mortality was elevated by nearly three times (pooled HR, 2.88; 95% CI, 1.38-6.01).
• Cardiovascular disease accounted for most deaths among patients with primary adrenal insufficiency who did not have congenital adrenal hyperplasia, whereas adrenal crisis accounted for most deaths among those with congenital adrenal hyperplasia.

IN PRACTICE:

"[The study] findings underline the need for optimization of GC [glucocorticoid] replacement therapy and improvement of residual risk management, such as cardiovascular prevention and prevention of adrenal crisis," the authors wrote.

SOURCE:

This study was led by Konstantinos Dalakas, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. It was published online on September 12, 2025, in the European Journal of Endocrinology.

LIMITATIONS:

The meta-analysis exhibited high heterogeneity, which limited the comparability of studies and warranted cautious interpretation. Preplanned analyses of time trends and causes of death were not feasible due to insufficient data. Most studies were conducted in Scandinavian countries or the UK, potentially limiting generalisability.

DISCLOSURES:

This study was supported by the Swedish government through the ALF agreement. Some authors reported serving as consultants, receiving lecture fees, and having other ties with pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.